Effects of immunotherapy on experimental immunodeficiency-related lymphoproliferative disease.

ABSTRACT

BACKGROUND: Human lymphokine-activated cells (LAK cells) and interferon alpha (IFN-alpha) have been used clinically in the therapy of posttransplant lymphoproliferative disease (PTLD). However, the efficacy of such therapy has not been extensively tested under controlled experimental conditions. METHODS: A B-cell line, derived from PTLD tissue and clonally related to the parent lesion, was tested for its response to IFN-alpha in vitro. The effects of LAK cells and IFN-alpha therapy were examined in a severe combined immunodeficiency disease (SCID) mouse model in vivo. RESULTS: The PTLD cell line studied showed a 30% decrease in the rate of growth upon incubation with 500 U/ml of IFN-alpha. This in vitro response was also reproduced in vivo, in tumor therapy studies conducted in SCID mice. The magnitude of this inhibitory effect in vivo was a function of tumor burden and dose of IFN-alpha. In parallel experiments, LAK cells reduced the tumorigenicity of a lymphoblastoid cell line derived from the peripheral blood of a patient with PTLD, and prolonged the survival of SCID-beige mice with established lymphoproliferative disease. In contrast with two prior studies, in which the use of autologous cytotoxic T cells was found to be necessary, we found the administration of third-party non-HLA-matched LAK cells also to be effective in reducing tumor burden. CONCLUSIONS: These observations demonstrate the efficacy of immunotherapy for lymphoproliferative disease under controlled experimental conditions, and validate currently ongoing efforts exploring the utility of such therapy in the clinical setting.